Evidence map›Paper›PMID 18755353›Full record

Trial reportJournal of the American College of Cardiology2008

The peroxisome proliferator-activated receptor-gamma agonist pioglitazone represses inflammation in a peroxisome proliferator-activated receptor-alpha-dependent manner in vitro and in vivo in mice.

Gabriela Orasanu, Ouliana Ziouzenkova, Pallavi R Devchand, Vedika Nehra, Osama Hamdy, Edward S Horton, Jorge Plutzky

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of the American College of Cardiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Gabriela OrasanuCardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Ouliana Ziouzenkova
Pallavi R Devchand
Vedika Nehra
Osama Hamdy
Edward S Horton
Jorge Plutzky
Brigham and Women's Hospital · USJoslin Diabetes Center · US

Funding

Lipolytic Mechanisms of PPAR ActivationR01HL071745 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI PLUTZKY, JORGE · 2004 to 2007
$1.6M
NHLBI NIH HHS R01 HL071745
6 · The paper itself

Abstract

objectivesOur aim was to investigate if the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone modulates inflammation through PPARalpha mechanisms.

backgroundThe thiazolidinediones (TZDs) pioglitazone and rosiglitazone are insulin-sensitizing PPARgamma agonists used to treat type 2 diabetes (T2DM). Despite evidence for TZDs limiting inflammation and atherosclerosis, questions exist regarding differential responses to TZDs. In a double-blinded, placebo-controlled 16-week trial among recently diagnosed T2DM subjects (n = 34), pioglitazone-treated subjects manifested lower triglycerides and lacked the increase in soluble vascular cell adhesion molecules (sVCAM)-1 evident in the placebo group. Previously we reported PPARalpha but not PPARgamma agonists could repress VCAM-1 expression. Since both triglyceride-lowering and VCAM-1 repression characterize PPARalpha activation, we studied pioglitazone's effects via PPARalpha.

methodsPioglitazone effects on known PPARalpha responses--ligand binding domain activation and PPARalpha target gene expression--were tested in vitro and in vivo, including in wild-type and PPARalpha-deficient cells and mice, and compared with the effects of other PPARgamma (rosiglitazone) and PPARalpha (WY14643) agonists.

resultsPioglitazone repressed endothelial TNFalpha-induced VCAM-1 messenger ribonucleic acid expression and promoter activity, and induced hepatic IkappaBalpha in a manner dependent on both pioglitazone exposure and PPARalpha expression. Pioglitazone also activated the PPARalpha ligand binding domain and induced PPARalpha target gene expression, with in vitro effects that were most pronounced in endothelial cells. In vivo, pioglitazone administration modulated sVCAM-1 levels and IkappaBalpha expression in wild-type but not PPARalpha-deficient mice.

conclusionsPioglitazone regulates inflammatory target genes in hepatic (IkappaBalpha) and endothelial (VCAM-1) settings in a PPARalpha-dependent manner. These data offer novel mechanisms that may underlie distinct TZD responses.

Indexed as

AnimalsDiabetes Mellitus, Type 2Double-Blind MethodEndothelinsFemaleHumansHypoglycemic AgentsInflammationIn Vitro TechniquesMaleMiceMiddle AgedPioglitazonePPAR alphaPPAR gammaRosiglitazoneEndothelinsHypoglycemic AgentsPioglitazonePPAR alphaPPAR gammaRosiglitazoneThiazolidinedionesTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1

Identifiers

PMID18755353
PMCPMC2633943
OpenAlexW2030921297

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.